15-73951937-C-G

Variant names:

• chr15-73951937-C-G
• rs8818
• NM_005576.4:c.*100C>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005576.4(LOXL1):​c.*100C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.771 in 1,155,798 control chromosomes in the GnomAD database, including 347,430 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.70 (38791 hom., cov: 33)
  • Exomes 𝑓: 0.78 (308639 hom.)
• Consequence: LOXL1 NM_005576.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.513
• Publications: 19 publications found

Genes affected

LOXL1 (HGNC:6665): (lysyl oxidase like 1) This gene encodes a member of the lysyl oxidase family of proteins. The prototypic member of the family is essential to the biogenesis of connective tissue, encoding an extracellular copper-dependent amine oxidase that catalyzes the first step in the formation of crosslinks in collagen and elastin. The encoded preproprotein is proteolytically processed to generate the mature enzyme. A highly conserved amino acid sequence at the C-terminus end appears to be sufficient for amine oxidase activity, suggesting that each family member may retain this function. The N-terminus is poorly conserved and may impart additional roles in developmental regulation, senescence, tumor suppression, cell growth control, and chemotaxis to each member of the family. Mutations in this gene are associated with exfoliation syndrome. [provided by RefSeq, Jan 2016]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LOXL1	NM_005576.4	c.*100C>G		3_prime_UTR_variant	Exon 7 of 7	ENST00000261921.8	NP_005567.2
LOXL1	XM_017022179.2	c.*100C>G		3_prime_UTR_variant	Exon 7 of 7		XP_016877668.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LOXL1	ENST00000261921.8	c.*100C>G		3_prime_UTR_variant	Exon 7 of 7	1	NM_005576.4	ENSP00000261921.7
LOXL1	ENST00000562548.1	n.910C>G		non_coding_transcript_exon_variant	Exon 3 of 3	2
LOXL1	ENST00000567675.1	n.261C>G		non_coding_transcript_exon_variant	Exon 3 of 3	3
LOXL1	ENST00000566011.5	n.*713C>G		downstream_gene_variant		5		ENSP00000457827.1

Frequencies

GnomAD3 genomes AF: 0.701 AC: 106660 AN: 152062 Hom.: 38761 Cov.: 33

Gnomad AFR AF: 0.507

Gnomad AMI AF: 0.789

Gnomad AMR AF: 0.790

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.618

Gnomad SAS AF: 0.643

Gnomad FIN AF: 0.784

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.796

Gnomad OTH AF: 0.693

GnomAD4 exome AF: 0.782 AC: 784402 AN: 1003620 Hom.: 308639 Cov.: 13 AF XY: 0.779 AC XY: 381062 AN XY: 489078

African (AFR) AF: 0.499 AC: 10613 AN: 21266

American (AMR) AF: 0.786 AC: 9676 AN: 12316

Ashkenazi Jewish (ASJ) AF: 0.726 AC: 10455 AN: 14408

East Asian (EAS) AF: 0.649 AC: 18108 AN: 27914

South Asian (SAS) AF: 0.644 AC: 23736 AN: 36856

European-Finnish (FIN) AF: 0.787 AC: 26026 AN: 33064

Middle Eastern (MID) AF: 0.614 AC: 1702 AN: 2770

European-Non Finnish (NFE) AF: 0.803 AC: 653565 AN: 813980

Other (OTH) AF: 0.744 AC: 30521 AN: 41046

GnomAD4 genome AF: 0.701 AC: 106738 AN: 152178 Hom.: 38791 Cov.: 33 AF XY: 0.701 AC XY: 52152 AN XY: 74412

African (AFR) AF: 0.507 AC: 21070 AN: 41524

American (AMR) AF: 0.790 AC: 12091 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.727 AC: 2524 AN: 3472

East Asian (EAS) AF: 0.618 AC: 3185 AN: 5156

South Asian (SAS) AF: 0.643 AC: 3103 AN: 4824

European-Finnish (FIN) AF: 0.784 AC: 8319 AN: 10606

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.796 AC: 54082 AN: 67972

Other (OTH) AF: 0.694 AC: 1465 AN: 2112

Alfa AF: 0.741 Hom.: 5298

Bravo AF: 0.693

Asia WGS AF: 0.592 AC: 2057 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	14
DANN	Benign	0.79
PhyloP100		0.51
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs8818; hg19: chr15-74244278;